Recently, much attention is paid to an in situ hybridization by a DNA chip to perform prevention and diagnosis of diseases. This is made by placing a fragment (cells) of a specified site of DNA in a matrix form on a glass base plate. The DNA chip is used in determining whether a tested person has a gene related to a specified disease or not by adding a fluorescent material to a sample such as blood that is extracted from the tested person to label the DNA of the sample, and bringing the sample and the cells on the DNA chip in contact with each other to perform hybridization, and the like.
Conventionally, when it is detected with which cell of the DNA chip the DNA in the sample creates a hybrid, a device called a DNA chip reader as shown in FIG. 11 is used to detect it. The DNA chip reader 10 is a so-called confocal type, and includes a laser light source 14 for irradiating a DNA chip (specimen) 12 placed on an inspection stage not irradiated with laser light. A condenser lens 16 and a pin-hall 18 are placed in series under the laser light source 14 to concentrate a laser beam 21 emitted by the laser light source 14.
The laser beam 21, which passes through the pin-hole 18, is transmitted through a dichroic mirror 22 to separate fluorescence emitted from the DNA chip 12 and the laser beam 21, and thereafter, it is made parallel light by a collimate lens 24. After the laser beam 21, which is made parallel light by the collimate lens 24, is reflected by a pair of galvano mirrors 26 and 28, it is incident on an objective lens 30, and converges on the DNA chip 12 to irradiate to the cells. The galvano mirrors 26 and 28 are for scan-running the laser beam 21 along a surface of the DNA chip 12, and for example, when the galvano mirror 26 is rotated, the laser beam 21 moves in an X-direction on the surface of the DNA chip 12, and when the galvano mirror 28 is rotated, the laser beam 21 moves in a Y-direction. Accordingly, by controlling the rotation of the galvano mirrors 26 and 28, the laser beam 21 can irradiate to optional cells placed in the matrix form on the DNA chip 12.
When the cell of the DNA chip 12 creates a hybrid with the DNA in the sample labeled by the fluorescent material, it emits fluorescence when it is irradiated with the laser beam 21. The fluorescence emitted from this cell is incident on the dichroic mirror 22 via the objective lens 30, the galvano mirrors 28 and 26, and the collimate lens 24. The dichroic mirror 22 selectively deflects only the incident fluorescence at 90 degrees to make it incident on the photoelectron multiplier tube 34 via the pin-hole 32. The photoelectron multiplier tube 34 generates photoelectrons with the incident fluorescence, and amplifies them to output them as a voltage pulse. Accordingly, by monitoring the output of the photoelectron multiplier tube 34, it can be known which cell of the DNA chip 12 emits the fluorescence, that is, it can be known that the gene that creates a hybrid with that cell is included in the sample.
However, the above-described conventional DNA chip reader 10 needs to scan the surface of the DNA chip 12 by moving the laser beam 21 in a step form. For this reason, when the laser beam 21 is scan-moved along the surface of the DNA chip 12 in which N×N of cells are placed in a matrix form, the scanning time is increased exponentially when the number of N increases to 100 to 1000 (the number of cells is ten thousand to a million), and thus tremendous time is required to read the information of the cells. Consequently, there is a trial to place multiple photoelectric multiplier tubes 34 in a plane, irradiate the entire DNA chip 12 with a laser beam, and read output pulse of each of the photoelectric multiplier tubes 34 at once to obtain two-dimensional information, but this is not realistic because the photoelectron multiplier tube 34 is expensive and a large installation space is required.
It is considered to use a CCD type photon counting video camera to obtain the position of the cell, which creates a hybrid of the DNA chip 12 two-dimensionally. The CCD type photon counting video camera performs photoelectric conversion of incident photons to generate photoelectrons, amplifies a photoelectron in the number of electrons in each capillary (channel) by a secondary electron amplification, called a microchannel plate (MCP) constituted by a number of capillaries (capillaries), make them incident on the fluorescent material again to convert the electrons into light, and receive the converted light with the CCD video camera. However, when the CCD type photon counting video camera is used, the following problem arises.
The processing of the photon counting mode is performed for a signal from the CCD video camera. Namely, an output signal of the CCD element, which corresponds to each pixel (pixel) of the CCD video camera is binarized, and the output signals (the number of incident photons) per unit time are counted. However, readout of the output signals for each element of the CCD video camera is no more than about 100 times/s.
On the other hand, the fluorescence occurring from the cells of the DNA chip 12 is extremely weak, and photons are rarely incident on each channel (capillary) of the MCP. In addition, the duration of the pulse of the electrons incident on the CCD element from the MCP is 0.1 to 10 ns, which is exceedingly short. Consequently, each element of the CCD video camera integrates the pulse of the electrons corresponding to the incident photons that rarely come for about 10 ms being a read cycle of the signal, which is 106 to 108 times as long as the pulse duration of the electrons. However, the CCD has a noise called a dark current, this noise is also integrated during the read cycle, and the detection system cannot be realized unless the S/N of the pulse is 106 to 108 or more, which is unpractical.
The present invention is made to eliminate the disadvantages of the aforementioned prior art, and has its object to make it possible to detect two-dimensional weak radiation at a high speed with high precision.
The present invention has another object to make it possible to obtain a two-dimensional color image based on weak radiation with ease.